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Updated: Jan 11, 2026

Isolation and Direct Neuronal Reprogramming of Mouse Astrocytes

Isolation and Direct Neuronal Reprogramming of Mouse Astrocytes

Published on: July 7, 2022

Decoding transcriptional identity during neuron-astroglia cell fate driven by RAR-specific agonists.

Ariel Galindo-Albarrán¹, Aysis Koshy¹, Maria Grazia Mendoza-Ferri¹

¹UMR 8030 Génomique Métabolique, Genoscope, Institut François Jacob, CEA, CNRS, University of Evry-val-d'Essonne, University Paris-Saclay, 91057 Évry, France.

NAR Molecular Medicine

|November 19, 2025

Summary

This summary is machine-generated.

Retinoic acid signaling via retinoic acid receptors (RARs) drives stem cell differentiation into diverse neural cell types. Spatially resolved transcriptomics in brain organoids reveals RAR isotype roles in specialized nervous tissue formation.

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Area of Science:

Developmental Biology
Neuroscience
Stem Cell Biology

Background:

Cellular differentiation into specific lineages is crucial for organ and tissue formation.
Retinoic acid (RA) signaling, mediated by nuclear receptors (Retinoid X Receptor/Retinoic Acid Receptor - RXR/RAR), is a key morphogen in nervous system development and brain homeostasis.

Purpose of the Study:

To investigate the role of specific retinoic acid receptor (RAR) agonists in driving mouse stem cell differentiation into neural lineages.
To elucidate the spatial and temporal effects of RAR activation on nervous tissue formation in brain organoids.

Main Methods:

Single-cell RNA sequencing of approximately 80,000 cells during 16 days of monolayer stem cell differentiation.
Spatially resolved transcriptomics analysis of over 8,000 regions across 28 brain organoids cultured for 90 days.
Treatment with pan-RAR agonist (all-trans retinoic acid), RARα agonist (BMS753), and RARβ/RARγ agonists (BMS641 + BMS961).

Main Results:

RAR-specific agonists successfully induced differentiation into various neuronal subtypes, astrocytes, and oligodendrocyte precursors.
Spatially resolved transcriptomics identified distinct RAR isotype expression patterns within organoids.
These patterns correlated with specialization signatures in mature tissues, including retina-like structures and microglia.

Conclusions:

Specific RAR signaling pathways can direct stem cell differentiation towards distinct neural lineages.
Spatial expression of RAR isotypes contributes to the specialization of neural tissues within brain organoids.
This study provides insights into the molecular mechanisms governing neural development and homeostasis through retinoid signaling.